Heart failure is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with blood or pump a sufficient amount of blood through the body. It is not to be confused with “cessation of heartbeat”, which is known as asystole, or with cardiac arrest, which is the cessation of normal cardiac function with subsequent hemodynamic collapse leading to death.
Congestive heart failure is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly when the condition is considered “mild”. Even with the best therapy, heart failure is associated with an annual mortality of 10%. It is the leading cause of hospitalization in people older than 65.
Heart failure is characterized by clinical signs and symptoms secondary to the inadequate response to the body metabolic requirements. This condition could occur acutely or have a chronic course.
The pathophysiological interpretations of heart failure have had a remarkable evolution in time. This syndrome was considered as a pump deficiency associated with a renal dysfunction in years '50-'60, a pump dysfunction associated with an increase in peripheral resistance in years '70-'80 and is considered at present as a failure of the pump function associated with the neuro-hormonal activation with resulting hemodynamic impairments which take to a dysfunction of many organs and apparatuses.
The present drug therapy of cardiac “pump function” includes the use of drugs acting by various modes of action on different points of the etiopathogenesis of the diseases.
Non-limiting examples of such drugs are: ACE-inhibitors (Angiotensin Converting Enzymes inhibitors), diuretics, non-digitalis positive inotropic drugs such as adrenergics and inhibitors of phosphodiesterase, arteriolar and venular vasodilators, e.g. hydralazine and isosorbide dinitrate, beta-blockers e.g. metoprolol and bisoprolol and digitalis derivatives, e.g. digitoxin.
The ageing of the population seems to be a contributing factor to amplify the relevance of the phenomenon.
WO 02/058793 relates to the use of polyunsaturated fatty acid for the prevention or treatment of heart failure. No experimental data are provided in this application.
Lancet 1999 (354: 447-55) (GISSI-Prevenzione clinical trial) relates to the reduction of total mortality in post-myocardial infarction patients treated with n-3 PUFA for 3.5 years.
EP1310249 relates to the use of polyunsaturated fatty acid for the primary prevention of major cardiovascular events in patients, who have not undergone previous infarct episodes. However only some animal data are reported in the patent application and these are not necessarily predictive of the drug efficacy in the treatment of HF in humans.
WO 89/11521 describes an industrial process for the extraction of mixtures having a high content in poly-unsaturated acids useful in the treatment of cardiovascular pathologies.
U.S. Pat. No. 5,502,077, U.S. Pat. No. 5,656,667, U.S. Pat. No. 5,698,594 and IT 1235879, refer respectively to hypertriglyceridemia, defects of the cholesterol level and hypertension. However, each of the cited documents deal with the treatment of risk factors, not with real and proclaimed illnesses.
U.S. Pat. No. 5,753,703 describes the use of L-carnitine or its derivatives in association with polyunsaturated fatty acids of the omega-3 series or their esters, in particular EPA and DHA, for the prevention and treatment of cardiovascular disorders, vascular pathologies, diabetic peripheral neuropathies, and atherosclerotic, thromboembolytic and tissue disorders.
EP0409903 describes a process for preparing high concentration mixtures of EPA and DHA and/or their esters useful for treating hyperlipemia and related pathologies, thrombosis, cardiac infarct, platelet aggregation, as anticoagulants in the prevention of atherosclerosis, for the treatment of cerebral infarct, of lesions and occlusions caused by vasomotor spasms, of diabetes and its complications, of chronic and acute inflammations, of autoimmune symptoms, in the prevention of side effects caused by non-steroid anti-inflammatories at the gastrointestinal level and in tumour prevention.
CN 1082909 describes compositions based on ethyl esters of EPA and DHA and other polyunsaturated fatty acids of the omega-3 series in association with soya phospholipids, oenothera odorata and ginkgetin, as antithrombotic and antidementia agents for treating for example dementia and infarct of the myocardium.
U.S. Pat. No. 5,760,081 describes a method for preventing imminent fibrillation of the myocardial ventricle by intravenous infusion of a composition containing EPA, where the subject at risk of imminent fibrillation has already often been the protagonist of an episode of infarct of the myocardium and where the infusion is effected within 3 hours of the infarct episode, possibly using intracardiac injection. These are always situations of extreme emergency and of parenteral intervention, for the specific treatment of ventricular fibrillation.
Clinical Drug Investigation 15 (6), 473 relates to the administration of EPA and DHA ethyl esters, at a dose of 4 g per day for decreasing triglycerides and total apolipoprotein C III and increasing antithrombin III, in subjects with abnormal plasmatic lipoprotein symptoms and have undergone an infarct of the myocardium, they having consequently suggested that an administration of these compositions can result in an improvement in the lipoprotein level and hence a decrease in the relative risk factors.
WO 00/48592 describes the use of a mixture of EPA and DHA ethyl esters in quantities greater than 25% b.w., for preventing death, in particular “sudden death” in patients who have already suffered an infarct of the myocardium.
In the medical field there is still the need of a safe and convenient method for the prevention of deaths, the reduction of the total hospitalisations or the hospitalisations for a cardiovascular reason in patients with heart failure.